Alterations in immunoglobulin levels in uninfected children born to HIV infected women

Background Immunoglobulin levels are known to be elevated in HIV infected children. However, little is known about the effect of maternal HIV infection and the maternal altered immune system on immunoglobulin levels in uninfected children. As few data are available on immunoglobulins from young healthy children, we used data from uninfected children born to hepatitis C virus (HCV) infected women as a comparison. Methods Prospective data on immunoglobulin levels were available from birth to 5 years for children enrolled in the European Collaborative Study (ECS) of children born to HIV-1 infected women and from birth to 24 months for children enrolled in the European Paediatric HCV Network (EPHN). Children born to HIV/HCV co-infected women were excluded. Smoothers (running means) illustrated patterns of immunoglobulins over age by infection status. Associations between infant and maternal factors and child log10 total IgG, IgM and IgA levels were quantified in linear regression analyses allowing for repeated measures within child. Further analyses were performed using only data of HIV exposed uninfected children to investigate associations between child immunoglobulins and maternal immunological and virological factors and anti-retroviral therapy exposure. Results 1751 HIV uninfected, 190 HIV infected children (ECS), 173 HCV uninfected and 30 HCV infected children (EPHN) were included. HIV infected children had higher levels of all immunoglobulins compared to uninfected children over all ages. HIV uninfected children had significantly higher IgG, IgM and IgA levels than HCV uninfected children upto at least 24 months, adjusting for gender, prematurity and race. Prematurity was associated with significantly lower levels of immunoglobulins upto 24 months. Children born to African women had higher IgG and IgA levels upto 24 months than those born to white women but lower IgM in the first 6 months. Among HIV uninfected children higher IgG levels were associated with elevated maternal IgG levels, as well for measurements from 18 months to 5 years of age. No significant effect of maternal CD4 count was observed. ART exposure was associated with significantly lower IgG levels at 6-24 months. Race was not associated with immunoglobulin levels in multivariable analyses in this sub-group. Conclusions These findings indicate significant alterations in immunoglobulin levels in uninfected children born to HIV infected women. This suggests that exposure to an activated maternal immune system is associated with an altered humoral response in children without antigen stimulation, and warrants further research

The role of impulse parameters in force variability

One of the principle limitations of the human motor system is the ability to produce consistent motor responses. When asked to repeatedly make the same movement, performance outcomes are characterized by a considerable amount of variability. This occurs whether variability is expressed in terms of kinetics or kinematics. Variability in performance is of considerable importance because for tasks requiring accuracy it is a critical variable in determining the skill of the performer. What has long been sought is a description of the parameter or parameters that determine the degree of variability. Two general experimental protocals were used. One protocal is to use dynamic actions and record variability in kinematic parameters such as spatial or temporal error. A second strategy was to use isometric actions and record kinetic variables such as peak force produced. What might be the important force related factors affecting variability is examined and an experimental approach to examine the influence of each of these variables is provided

Successful paediatric HIV treatment in rural primary care in Africa

<p>Objective: Clinical outcomes of HIV-infected children on antiretroviral treatment (ART) in a decentralised, nurse/counsellor-led programme.</p> <p>Design: Clinical cohort.</p> <p>Setting: KwaZulu-Natal, South Africa.</p> <p>Patients: HIV-infected children aged <= 15 years on ART, June 2004-2008.</p> <p>Main outcome measures: Survival according to baseline characteristics including age, WHO clinical stage, haemoglobin and CD4%, was assessed in Kaplan-Meier analyses. Hazard ratios for mortality were estimated using Cox proportional hazards regression and changes in laboratory parameters and weight-for-age z scores after 6-12 months' treatment were calculated.</p> <p>Results: 477 HIV-infected children began ART at a median age of 74 months (range 4-180), median CD4 count (CD4%) of 433 cells/mm(3) (17%) and median HIV viral load of log 4.2 copies/ml; 105 (22%) were on treatment for tuberculosis and 317 (76.6%) were WHO stage 3/4. There were significant increases after ART initiation in CD4% (17% vs 22%; p<0.001), haemoglobin (9.9 vs 11.7 g/l; p <= 0.001) and albumin (30 vs 36 g/l; p <= 0.001). 32 (6.7%) children died over 732 child-years of follow-up (43.7 deaths/1000 child-years; 95% CI 32.7 to 58.2), 17 (53.1%) within 90 days of treatment initiation; median age of death was 84 (IQR 10-181) months. Children with baseline haemoglobin <= 8 g/l were more likely to die (adjusted HR 4.5; 95% CI 1.6 to 12.3), as were those aged <18 months compared with >60 months (adjusted HR 3.2; 95% CI 1.2 to 9.1).</p> <p>Conclusions Good clinical outcomes in HIV-infected children on ART are possible in a rural, decentralised service. Few young children are on ART, highlighting the urgent need to identify HIV-exposed infants.</p&gt

An Analysis of Kinetic Response Variability

Studies evaluating variability of force as a function of absolute force generated are synthesized. Inconsistencies in reported estimates of this relationship are viewed as a function of experimental constraints imposed. Typically, within-subject force variability increases at a negative accelerating rate with equal increments in force produced. Current pulse-step and impulse variability models are unable to accommodate this description, although the notion of efficiency is suggested as a useful construct to explain the description outlined

Hamara Healthy Living Centre - an evaluation

Hamara is a Healthy Living Centre which aims to improve health and well-being through providing a range of culturally appropriate activities and services. Hamara has a vision of 'bringing communities together' and since it was established in 2004, the Centre has provided a valuable community resource in South Leeds. Partnership work between Hamara and Leeds Met goes back to 2002. In 2007, the Centre for Health Promotion Research carried out an evaluation of Hamara in partnership with Hamara staff and Leeds Met Community Partnerships and Volunteering. This was followed by a highly successful community cohesion conference 'One Community' which was held at Hamara on 10th October 2008, and was supported through a Leeds Met public engagement grant. The event attracted over a hundred people from diverse communities and organisations across Leeds. A packed audience heard Hilary Benn, local MP and Patron of Hamara, talk about the importance of working in collaboration around community cohesion. Jane South, Centre for Health Promotion Research, presented the main evaluation results and set out the some challenges for the future. The proceedings concluded with the presentation of awards to a number of for local community champions who work to bring people together and make a real difference in the city of Leeds

Systematic derivation of a rotationally covariant extension of the 2-dimensional Newell-Whitehead-Segel equation

An extension of the Newell-Whitehead-Segel amplitude equation covariant under abritrary rotations is derived systematically by the renormalization group method.Comment: 8 pages, to appear in Phys. Rev. Letters, March 18, 199

Human resources needs for universal access to antiretroviral therapy in South Africa: a time and motion study

<p>Background - Although access to life-saving treatment for patients infected with HIV in South Africa has improved substantially since 2004, treating all eligible patients (universal access) remains elusive. As the prices of antiretroviral drugs have dropped over the past years, availability of human resources may now be the most important barrier to achieving universal access to HIV treatment in Africa. We quantify the number of HIV health workers (HHWs) required to be added to the current HIV workforce to achieve universal access to HIV treatment in South Africa, under different eligibility criteria.</p> <p>Methods - We performed a time and motion study in three HIV clinics in a rural, primary care-based HIV treatment program in KwaZulu-Natal, South Africa, to estimate the average time per patient visit for doctors, nurses, and counselors. We estimated the additional number of HHWs needed to achieve universal access to HIV treatment within one year.</p> <p>Results - For universal access to HIV treatment for all patients with a CD4 cell count of ≤350 cells/μl, an additional 2,200 nurses, 3,800 counselors, and 300 doctors would be required, at additional annual salary cost of 929 million South African rand (ZAR), equivalent to US$141 million. For universal treatment (‘treatment as prevention’), an additional 6,000 nurses, 11,000 counselors, and 800 doctors would be required, at an additional annual salary cost of ZAR 2.6 billion (US$ 400 million).</p> <p>Conclusions - Universal access to HIV treatment for patients with a CD4 cell count of ≤350 cells/μl in South Africa may be affordable, but the number of HHWs available for HIV treatment will need to be substantially increased. Treatment as prevention strategies will require considerable additional financial and human resources commitments.</p&gt

The art of HIV elimination: past and present science

Introduction: Remarkable strides have been made in controlling the HIV epidemic, although not enough to achieve epidemic control. More recently, interest in biomedical HIV control approaches has increased, but substantial challenges with the HIV cascade of care hinder successful implementation. We summarise all available HIV prevention methods and make recommendations on how to address current challenges. Discussion: In the early days of the epidemic, behavioural approaches to control the HIV dominated, and the few available evidence-based interventions demonstrated to reduce HIV transmission were applied independently from one another. More recently, it has become clear that combination prevention strategies targeted to high transmission geographies and people at most risk of infections are required to achieve epidemic control. Biomedical strategies such as male medical circumcision and antiretroviral therapy for treatment in HIV-positive individuals and as preexposure prophylaxis in HIV-negative individuals provide immense promise for the future of HIV control. In resourcerich settings, the threat of HIV treatment optimism resulting in increased sexual risk taking has been observed and there are concerns that as ART roll-out matures in resource-poor settings and the benefits of ART become clearly visible, behavioural disinhibition may also become a challenge in those settings. Unfortunately, an efficacious vaccine, a strategy which could potentially halt the HIV epidemic, remains elusive. Conclusion: Combination HIV prevention offers a logical approach to HIV control, although what and how the available options should be combined is contextual. Therefore, knowledge of the local or national drivers of HIV infection is paramount. Problems with the HIV care continuum remain of concern, hindering progress towards the UNAIDS target of 90-90-90 by 2020. Research is needed on combination interventions that address all the steps of the cascade as the steps are not independent of each other. Until these issues are addressed, HIV elimination may remain an unattainable goal

Rapid testing may not improve uptake of HIV testing and same day results in a rural South African community: a cohort study of 12,000 women

<p>Background: Rapid testing of pregnant women aims to increase uptake of HIV testing and results and thus optimize care. We report on the acceptability of HIV counselling and testing, and uptake of results, before and after the introduction of rapid testing in this area.</p> <p>Methods and Principal Findings: HIV counsellors offered counselling and testing to women attending 8 antenatal clinics, prior to enrolment into a study examining infant feeding and postnatal HIV transmission. From August 2001 to April 2003, blood was sent for HIV ELISA testing in line with the Prevention of Mother-to-Child Transmission (PMTCT) programme in the district. From May 2003 to September 2004 women were offered a rapid HIV test as part of the PMTCT programme, but also continued to have ELISA testing for study purposes. Of 12,323 women counselled, 5,879 attended clinic prior to May 2003, and 6,444 after May 2003 when rapid testing was introduced; of whom 4,324 (74.6%) and 4,810 (74.6%) agreed to have an HIV test respectively. Of the 4,810 women who had a rapid HIV test, only 166 (3.4%) requested to receive their results on the same day as testing, the remainder opted to return for results at a later appointment. Women with secondary school education were less likely to agree to testing than those with no education (AOR 0.648, p<0.001), as were women aged 21–35 (AOR 0.762, p<0.001) and >35 years (AOR 0.756, p<0.01) compared to those <20 years.</p> <p>Conclusions: Contrary to other reports, few women who had rapid tests accepted their HIV results the same day. Finding strategies to increase the proportion of pregnant women knowing their HIV results is critical so that appropriate care can be given.</p&gt

An integrated approach to improving the availability and utilisation of tuberculosis healthcare in rural South Africa

Background. Patients with tuberculosis (TB) face several challenges in accessing care, and an integrated service that includes HIV testingcould be preferable for them and ensure timely HIV treatment initiation and optimal TB care.Objectives. To investigate factors, including uptake of HIV testing, associated with availability and utilisation of healthcare by TB patientsin a rural programme devolved to primary care in Hlabisa sub-district, KwaZulu-Natal.Methods. Three hundred TB patients were randomly selected in a two-stage-sampling scheme with five primary healthcare clinic (PHC)sampling units selected with probability proportional to size. Data were collected using a structured questionnaire. We describe key availability and utilisation factors and analyse factors associated with being offered an HIV test in multiple regressions controlling for sex, age, education, employment and marital status.Results. Most patients (75.2%) received care for a first episode of TB, mainly pulmonary. Nearly all (94.3%) were offered an HIV test duringtheir current TB treatment episode, patients using their closest clinic being substantially more likely to have been offered HIV testing than those not using their closest clinic (adjusted odds ratio 12.79, p=0.05). About one-fifth (20.3%) of patients did not take medication under observation, and 3.4% reported missing taking their tablets at some stage. Average travelling time to the clinic and back was 2 hours, most patients (56.8%) using minibus taxis.Conclusion. We demonstrate high HIV testing rates among TB patients in a rural public programme, suggesting appropriate managementof HIV-TB co-infected patients. We describe healthcare availability and utilisation factors that can inform the proposed district managementteams for PHC re-engineering on areas needing improvement